Clear cell sarcomas of the kidney are characterised by <i><scp>BCOR</scp></i> gene abnormalities, including exon 15 internal tandem duplications and <i><scp>BCOR</scp>–<scp>CCNB</scp>3</i> gene fusion

Wong, Ming Keong; Ng, Cedric Chuan Young; Kuick, Chik Hong; Aw, Sze Jet; Rajasegaran, Vikneswari; Lim, Jing Quan; Jain, Sudhanshi; Loh, Eva; Yin, Minzhi; Ma, Jing; Zhang, Zhongde; Iyer, Prasad; Loh, Amos Hong Pheng; Duan, Lian; Wang, Shi; Goh, Shaun Giap Hean; Lim, Tse Hui; Lim, Alvin Soon Tiong; Ng, Tony; Goytain, Angela; Loh, Alwin Hwai Liang; Tan, Puay Hoon; Teh, Bin Tean; Chang, Kenneth Tou En

doi:10.1111/his.13366

Cited by 61 publications

(68 citation statements)

References 53 publications

(82 reference statements)

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“…Two of the cases primary to the kidney occurred at ages 26 and 46 years, much older than the 3 BCOR-CCNB3 sarcomas previously reported at this location (8-12 years). 3,14,15 There is a controversy as to whether renal BCOR-CCNB3 sarcoma should be viewed as a variant of CCSK or as visceral involvement of soft tissue sarcoma. 3,14,15 Although this question may be only semantic, our data may support the latter interpretation, because adult occurrence (>20 years) of CCSK is much rarer than BCOR-CCNB3 sarcomas (2/334 = 0.6% in CCSK 25 versus 7/92 = 7.6% for BCOR-CCNB3 sarcoma [1][2][3][4]6 ).…”

Section: Discussionmentioning

confidence: 99%

“…BCOR ITD is present in the great majority of clear cell sarcomas of the kidney (CCSK), 12,13 and BCOR-CCNB3 is found in rare kidney sarcomas in older children. 14,15 ZC3H7B-BCOR and BCOR ITD define unique subsets of high-grade endometrial stromal sarcoma (ESS) mostly in adults. [16][17][18] BCOR ITD characterizes a subset of high-grade neuroepithelial tumors, mostly in children, [19][20][21] and EP300-BCOR defines a subset of pediatric glioma.…”

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confidence: 99%

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Expanding the clinicopathologic and molecular spectrum of BCOR‐associated sarcomas in adults

Yoshida

Arai²,

Hama³

et al. 2020

Histopathology

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Aims BCOR gene alteration is a genetic signature of rare subsets of sarcomas. Most BCOR‐associated sarcomas thus far reported are in the pediatric population, except for uterine sarcomas. We studied seven cases of BCOR‐associated non‐uterine sarcomas in adult patients. Methods and results The patients were four men and three women ranging from 26 to 71 years in age. Three tumors, two of which primarily affected the kidney, showed BCOR‐CCNB3. One tumor with a ZC3H7B‐BCOR occurred in the chest wall, and a tumor with a novel CIITA‐BCOR was found in the sinonasal tract. Two tumors in the lung and breast harbored exon 15 internal tandem duplications of BCOR, a highly unexpected observation in this age group. All seven sarcomas consisted of dense proliferations of uniform round to spindle cells with fine chromatin within vascular stroma. BCOR‐CCNB3 sarcomas showed swirling fascicular growth. The tumor with the ZC3H7B‐BCOR fusion showed a multinodular growth of spindle cells, and the tumors with the CIITA‐BCOR fusion showed palisading of oval cells. Both tumors with BCOR internal tandem duplication demonstrated nested to palisading growth of round cells within sclerotic non‐myxoid stroma. All seven sarcomas diffusely expressed BCOR and SATB2 immunohistochemically, with all three BCOR‐CCNB3 sarcomas being immunopositive for CCNB3. BCOR alterations were confirmed by RNA sequencing, polymerase chain reaction, Sanger sequencing, and/or fluorescence in situ hybridization. Conclusions This study expands the clinicopathologic and molecular spectrum of BCOR‐associated sarcomas, and emphasizes the importance of being aware of this entity in the differential diagnosis of adult non‐uterine sarcomas.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Expanding the clinicopathologic and molecular spectrum of BCOR‐associated sarcomas in adults

Yoshida

Arai²,

Hama³

et al. 2020

Histopathology

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“…BCOR‐CCNB3 fusion is seen mostly in males with a predilection for older children and adolescents . Furthermore, the tumors are seen mostly in bone and soft tissue . BCOR‐ITD and YWHAE‐NUTM2 is seen in younger children (<4 years of age) .…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the majority of BCOR‐CCNB3 sarcomas receive Ewing sarcoma–based therapy with a 5‐year survival rate of 72% . Given BCOR‐CCNB3 sarcomas share similar transcriptomic profiles with BCOR‐ITD–positive CCSK and patients with CCSK demonstrated improved outcome with doxorubicin‐based chemotherapy, we may consider treating BCOR‐CCNB3 sarcomas with CCSK‐based therapy . Remarkable similarity in clinical presentation and chemotherapy response in both patients makes it imperative that more patients with BCOR‐CCNB3 fusion CCSK should be identified and their clinical features should be defined.…”

Section: Discussionmentioning

confidence: 99%

“…A minority of patients with CCSK do not have BCOR‐ITD or YWHAE‐NUTM2B/E fusion . Other molecular abnormalities have been reported in these patients, including one patient with EGFR (epidermal growth factor receptor) ITD and three patients with BCOR‐CCNB3 (where CCNB3 is cyclin B3) fusion joining 5′ partner BCOR to the 3′ partner CCNB3 (encoding the testis‐specific cyclin B3) that had been originally reported as a recurrent gene fusion in a subset of Ewing‐like undifferentiated soft tissue sarcomas . We report two additional patients with BCOR‐CCNB3 fusion‐positive CCSK who presented with advanced disease and had an excellent response to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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BCOR‐CCNB3 fusion‐positive clear cell sarcoma of the kidney

Han

Bertrand

Patel

et al. 2019

Pediatric Blood & Cancer

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Clear cell sarcoma of the kidney (CCSK) is the second most common malignant pediatric renal tumor. Two of the recurrent somatic alterations reported in CCSK are BCL‐6 corepressor (BCOR) internal tandem duplication (ITD) and YWHAE‐NUTM2B/E gene fusion. A minority of patients with CCSKs have other rare somatic alterations. We report two patients with CCSK showing BCOR‐CCNB3 (where CCNB3 is cyclin B3) fusion, who had similar clinical presentation of a large renal mass with tumor thrombus extending through the inferior vena cava into the right atrium and a favorable response to chemotherapy. We recommend BCOR‐CCNB3 fusion testing for all patients with CCSK who lack BCOR‐ITD or YWHAE‐NUTM2B/E gene fusions.

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Paediatric BCOR‐associated sarcomas with a novel long spliced internal tandem duplication of BCOR exon 15

Goh

Kuick

Sugiura

et al. 2022

The Journal of Pathology CR

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Clear cell sarcoma of the kidney (CCSK) and primitive myxoid mesenchymal tumour of infancy (PMMTI) are paediatric sarcomas that most commonly harbour internal tandem duplications (ITDs) of exon 15 of the BCOR gene, in the range of 87–114 base pairs (bp). Some cases, instead, have BCOR‐CCNB3 or YWHAE‐NUTM2 gene fusions. About 10% of cases lack any of these genetic alterations when tested by standard methods. Two cases of CCSK and one PMMTI lacking the aforementioned mutations were analysed using Archer FusionPlex technology. Two related BCOR exon 15 RNA transcripts with ITDs of lengths 388 and 96 bp were detected in each case; only the 388 bp transcript was identified when genomic DNA was sequenced. In silico analysis of this transcript revealed acceptor and donor splice sites indicating that, at the RNA level, the 388‐bp transcript was likely spliced to form the 96‐bp transcript. The results were confirmed by Sanger sequencing using primers targeting the ITD breakpoint. This novel and unusually long ITD segment is difficult to identify by DNA sequencing using typical primer design strategies flanking entire duplicated segments because it exceeds the typical read lengths of most sequencing platforms as well as the usual fragment lengths obtained from formalin‐fixed paraffin‐embedded material. As diagnosis of CCSK and PMMTI may be challenging by morphology and immunohistochemistry alone, it is important to identify mutations in these cases. Knowledge of this novel BCOR ITD is important in relation to primer design for detection by sequencing, and using RNA versus DNA for sequencing.

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Clear cell sarcomas of the kidney are characterised by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR–CCNB3 gene fusion

Cited by 61 publications

References 53 publications

Expanding the clinicopathologic and molecular spectrum of BCOR‐associated sarcomas in adults

Expanding the clinicopathologic and molecular spectrum of BCOR‐associated sarcomas in adults

BCOR‐CCNB3 fusion‐positive clear cell sarcoma of the kidney

Paediatric BCOR‐associated sarcomas with a novel long spliced internal tandem duplication of BCOR exon 15

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